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I’m excited to announce that our paper finally came out! This was my first corresponding author paper and also my first decision to publish in an open source journal (meaning you should be able to read it for free). This work is the culmination of what I’ve been doing for the past 2 years or so at PHRI as an independent researcher. The patent for it is submitted as well. Things have changed a lot for me very recently and left me wondering where to go with my career. I’m considering branching out on my own and sending applications for PI positions to various places. I’ll keep you all posted on how that process goes as well.

I apologize for holding up my writing this month. I wanted to mention the reason why: it has to do with submitting a patent for one of my projects. I thought this would be a good opportunity to explain a little bit of the process as I’ve experienced it. I had what was almost a 3 hour long conversation with our patent lawyer last week and got a few of the insights into the field of patent law and how it relates specifically to biomolecules. This is the first time I will do this but I feel it needs mentioning: I AM NOT a patent lawyer myself. Though you may like my opinions expressed on this blog please do not take any of what I say here as legal advice.

Patents have always been, and always will be, a source of contention and defensiveness amongst scientists. You can look back to famous examples such as the long patent battles between Thomas Edison and Nikola Tesla for one example (1). Another more recent battle that I’ve brought up before is the fight between The University of California at Berkeley and Harvard University over the rights to CRISPr (2). But perhaps the oldest opponent bioengineers and biochemists have in patent battles is nature itself. Our patent lawyer explained to me that the first hurdle to clear in patenting a molecule is determining whether or not it could be considered “A Product of Nature”. This is to say, to some extent, molecules that exist naturally cannot be patented. Imagine if someone held a patent on the 20 essential amino acids themselves or on the four nucleic acids that make up our DNA! In my non-legal opinion it’s completely unfair to allow someone to try to claim a patent on something our bodies make naturally. The ways to get around this involve, for instance, patenting a process to purify these compounds rather than the compounds themselves. The main point, however, is that to secure a patent you need to make something new or to find a new way to make something old. If you can prove you are not cheating nature then you get the Intellectual Property; you get to decide who makes this produce or uses this process

The power of Intellectual Property and Patent Law has driven the field of synthetic biology, Big Pharma, and yes, even my “Molecular Yoga”. Scripps Research Institute points out, “Natural products remain the best sources of drugs and drug leads, and this remains true today despite the fact that many pharmaceutical companies have deemphasized natural products research in favor of HTP screening of combinatorial libraries during the past 2 decades.” (3). Note their use of the phrase “drugs and drug leads. A drug lead, or more commonly called a lead compound, is a starting point for biomedical researchers. These molecules can be altered and changed to improve the drugs by way of increasing the drug’s binding strength or decreasing side-effects (4). As our patent lawyer pointed out: THAT is what you can patent, as long as you can prove that such changes and alterations were not obvious or already present in small quantities in nature. This is why pharmaceutical companies are focused on screening or rational design of lead compounds; it makes them more easily patentable.

My job, in helping to craft this patent, is to turn what written for an upcoming paper into a set of claims on the patent. Part my discussion last week was determining what we felt we could claim related to our molecules. How, specifically do these molecules work? How are these molecules made? What variations, if any, can exist? Biomolecular patents can have dozens, even hundreds of claims. The goal is to make a patent as broad as possible such that someone cannot easily infringe upon that patent. Would-be infringers might take your molecule and alter it in some nominal way and claim it as their own work. If you can secure a patent with strongly enforceable claims, you can make money off of them through licensing, which will help you fund future research

When I started down the road of becoming a scientist I didn’t make patenting my work one of my main goals. I wanted to create new molecules, things that were useful, but not necessarily things that would make me money. In my opinion, patenting your molecules should be a means to an end, a way to sustain your research. There are a few colleagues of mine who’ve made millions of dollars from patenting simple biomolecules. I imagine it’s hard to prevent yourself from becoming consumed by the drive to make money over the drive to conduct research. They seem to be doing well though. They funnel a lot of that money back into their own lab. This model works especially well for a soft-money driven research facility based on grant-funded rather than tenured positions (something I’d like to go into at a later date). I was involved in creating another patent as a graduate student, which was subsequently accepted as a provisional patent. It appears to me that his work will be heading in that direction as well. I will keep you up to date with my feelings on patents and hopefully this will serve as a good reminder to myself if my views ever change drastically.

Today I wanted to discuss how we see the responsibility of reviewers in science. Peer-review is an integral component of the scientific community. The ability to evaluate and critique the work of others is vitally important in science. I’ve sort of touched on this before when talking about skepticism in science. You can think of a scientific article as an argument that someone is presenting. They need to present the argument as a hypothesis and to defend that hypothesis with their data. At the same time, those reviewing the argument and the data need to be qualified enough to give an informative critique; they need to be peers. I’ll describe what I see as the “modern” style of peer review and then move on to what I see as the “new” style.

The “modern” style of peer review as I would call it has been in use since at least the mid-20th century. Scientific articles had been publish before this time, with editors themselves taking charge of reviewing manuscripts. In the 1950’s and 1960’s academia had grown to such a point where there was both a demand that colleagues be able to review papers in their field before publication and enough qualified people to efficiently outsource the review process (1). In this modern review process, the editor sends out the manuscript to individuals in the field. How these individuals are selected is still somewhat of a mystery to the public at large and, in my opinion, to most of the scientific community as well. Ideally, the reviewers are other scientists who have worked on the same topic or in the same scientific field. The reason for this could be twofold. For one you don’t need to provide as much background information to people already familiar with terms in the article under review, and for two you are much more likely to hold the attention and interests of people who can make connections to their own work.

There is, however, much of the criticism and concern surrounding modern peer-review. In modern peer-review the article authors are not supposed to know their reviewers. This sets up the perverse incentive for someone publishing a similar article to attack competing work unfairly or thwart it’s publication for their own interests. Alternatively, a collaborator might provide very kind review if the paper’s publication might lead to publications for themselves down the line. Most journals have mechanisms to prevent both of these from happening. When submitting an article you are allowed to list a few scientists who “you would not like to be considered for review”. The journal will also mention that you can submit “suggested reviewers” but they cannot be coauthors nor can they be individuals with whom you had professional dealing within the past 4-5 years (e.g. you didn’t write a grant together, you didn’t publish a paper together, you don’t co-advise students etc). These, of course, are just suggestions. The editor gets the final say on picking the reviewers, and they could send it to someone who will give a poor review no matter what. You will not know who the reviewers are during the process and you might never know who reviewed your article. I feel that this modern peer review style is becoming obsolete and that a new peer-review style is emerging.

There is a new style of peer-review emerging since the beginning of the 21st century: Open Review. This type of review has been gaining more mainstream acceptance with the rise of Open-access journals and sites like Publons, which track reviews and reviewer records (2). Under this type of review process everything is out in the open and accessible. All communications between the reviewers and the authors are known and even the identities of the reviewers are known. The content of the reviews will be available along with the article if it is accepted for publication. Additionally there are “post-publication” reviewer, which critique the article after it has been accepted. The goal of this type of review is to demystify the entire process and to facility better discussion about the scholarly merits of an article. The downsides are obvious: there is the threat of collusion, but some studies have shown that there is very little difference in the quality of reviews or the outcome when using an open peer review process as opposed to the more traditional process (3). By opening up the review process we can make the scientific merit of an article stand out even stronger and provide more confidence in the ability of the scientific community to promote good science.

The open peer-review process achieves what I believe should be the main goal of any reviewer: to help improve the scientific merit of an article. The traditional or modern way of thinking about publishing is that it is a battle. In this battle you have been “defeated” if you let a poor article be published so why not err on the side of caution and reject anything that seems even remotely suspect? While I see the value in being a “gate-keeper” as a reviewer I personally feel that stopping there is lazy. The reviewer is responsible for working with an author to improve their article and to strengthen the conclusion they have made about their hypothesis. It would be better to put yourself on the side of the author, to have high standards for yourself, and to ask what your experience and expertise can add to this article to make it a valuable contribution to the journal. With this in mind, open peer-review has to be the best method of fostering the author-reviewer relationship. As a society we seem to be moving ever more and more towards a need for openness and transparency in institutions as well. Having a clear, open review allows gives us confidence in the peer-review process and allows us to sniff out collusion or scientific misconduct. I would encourage everyone to take a look at some articles that have been reviewed under “open peer-review” and to decide for themselves what makes the most sense.

I, like many other scientists, participated in the March for Science this past month. Today I wanted to mention briefly my reasons for participating in the March. There are some good questions being raised in the scientific community about whether or not scientists should be involved in politics or influencing public policy. In my personal, humble, opinion people who think that science is “above politics” are full of themselves. We are all human beings, we all have our own goals and we want to have input on public policy because, by its nature, it affects us. I had the great opportunity last Friday to meet with Dr. Franklin Carrero-Martinez, the Deputy Science and Technology Adviser to the Secretary of State. Dr. Carrero is a scientist by training and one who is now heavily involved in helping the State Department determine what to do with scientific information. This does not mean hiding any information or presenting a biased view but it does mean forming an opinion and making a decision based on a fair reading of the facts. That’s what I was marching for, a fair reading of the facts. In the field of public policy, opinions should not be formed and then backed up with data after the fact. All facts should be debated and an opinion should be formed from that debate. Of course, new data can always help us to refine or even change our opinions. In my mind, however, the failure to form an opinion and failure to take decisive action is a failure in leadership. So again, I’ll call on everyone to please get involved in scientific research and to think about how it affects your daily life.

To add more flexibility to our platforms for conducting scientific research, perhaps it’s time that scientists here in the US take into consideration options abroad. This thought was spurred on by a recent trip I took to China. I had the opportunity to see some of the university system there and how it’s become quite international. Not only can the environment be friendly, but there is also the fact that China is spending the second most total money on R&D behind only the US(1) and has been heavily investing in a computing power that might soon outpace the United States (2). In a previous post I said scientific research is an inherently globalized enterprise. I think as the reputation for quality research increases in Asia this fact will only become clearer. Certainly there are some caveats to working abroad in a large bureaucracy such as China, namely greater amounts of corruption by some academics (3). Still, this is no reason to completely discount the possibility of US students moving outside of the US to conduct their research.

For those seriously considering moving out of the US, it’s important to consider how you’ll be perceived by the scientific community. Students from the US are, by and large, considered top tier in terms of academics. This means students going from the US to, for example, Europe or Asia are very valuable. These students will have some leverage getting a position as a research professor/post doc/grad student abroad. There is always the question, however, of coming back to the United States, if that is the ultimate goal. I haven’t heard much downside to people doing research abroad, especially at top tier universities such as Max Planck, Oxford, University of Tokyo, etc. A person who goes to a smaller institute might be plagued with the same prestige-bias that students who attend smaller universities in the United States suffer. This begs the question: if you want to study or do research at a smaller university, why not try moving abroad?

One last concern about researching abroad, however, is that the research funding systems might work drastically differently in other countries. A labmate from Poland told me that in her country there are barely any postdoc positions available. People either go straight from graduate school to being a professor or not at all. I’ve heard from others that there are similar concerns in other countries in Europe. Certain institutes use a model where the PI of the lab, rather than getting tenure, has a strict term limit for their time. This might the window for what may seem like an ideal position very narrow. Countries such as China strictly limit career movement from university to university. This could cause a problem if the situation in a lab sours. If you are considering moving from the US to another country to do research please do some research into how the academic system works in that country.

Thanks for reading this time. I hope I’ve given you something to think about and maybe at least an interest in looking into how research works in other countries. Regardless of what happens in the world, the pursuit of science will continue to happen all over the Earth. I would encourage you to become a part of it wherever you can!

This month I’ll be attending the 61st Annual Biophysical Society Meeting in New Orleans Louisiana. For some interesting info on Biophysics please check out the blog at: https://biophysicalsociety.wordpress.com/

I’m happy to say that I was able to publish what was the bulk of my PhD thesis work in the Journal of the American Chemical Society and that it is finally available. This work formed the initial basis of my ideas around Molecular Yoga, the ability to control the ways in which molecules can change conformation and activate certain functions. In short, we created a combinatorial library based on the membrane active, toxic peptide Super-Melittin (derived from Melittin from honeybee venom). This peptide has excellent antimicrobial and potent anti-cancer capabilities but it is very harmful to our own body’s cells as well. I believe that by changing just a few of the amino acids we could create a peptide that would be inactive at neutral pH but could fold into an alpha-helix and activate at a low pH. Low pH environments are often found in tumors and with fungi and bacteria, making it an good activating key for these peptides. We’re currently working to develop a patent for these exact purposes and some of my colleagues, Sarah and Elmer are still working very hard to improve these peptides further. Please give it a read and let me know what you think!

I have another announcement too. I’ll be reporting next month as part of the 61st Biophysical Society Meeting blog in New Orleans. I hope to use this as a way to bring science to the public and to help them to interact with the scientific community. Look for updates along these lines in the next few weeks! Thanks for reading!